Genetic eye disease is a leading cause of blindness among infants, children and adults.
Dr Mariya Moosajee is focused on:
Understanding the molecular basis of inherited eye disorders, in particular the genetics of retinal dystrophies and ocular maldevelopment such a microphthalmia, anophthalmia, ocular coloboma and anterior segment dysgenesis.
Establishing the genotype-phenotype relationship through clinical deep phenotyping studies to identify optimal therapeutic windows and outcome measures for clinical trials, patient risk stratification as significant rates of systemic disease association to ensure the appropriate multidisciplinary clinical pathways for best patient care.
Development of novel therapeutic approaches for genetic eye disease including nonsense suppression therapy (ataluren, PTC-derivatives, NB compounds and amlexanox) anti-apoptotic agents, and gene therapy using non-viral gene delivery systems including scaffold matrix attachment region (S/MAR) vectors.
Dr Moosajee has won over 30 international and national prizes and awards for her research and was the first ophthalmologist in the UK to receive the prestigious Wellcome Trust Clinical Research Development Fellowship, for which she was also awarded the Beit Prize for the best fellowship by the Wellcome Trust.
For her scientific publications visit: Pubmed.
Developing the use of small molecule drugs to treat nonsense-mediated genetic eye disease
Proof-of-concept studies testing the safety and efficacy of novel small molecule drugs, such as ataluren and designer aminoglycosides, on (i) in vivo models of genetic eye disease including ocular coloboma, microphthalmia, choroideremia, Lebers congenital amaurosis and retinitis pigmentosa; and (ii) in vitro patient cells including skin fibroblasts and induced pluripotent stem cell (iPSC) derived retinal pigment epithelium, photoreceptors and optic cups with the same ocular disease.
A molecular therapy that safely targets nonsense mutations has the potential to treat sight-threatening genetic eye disorders in a disease- and gene-independent approach. This will have far-reaching effects across Ophthalmology as most genetic eye diseases have no treatment available.
Moosajee M, Tracey-White D, Smart M, Weetall M, Torriano S, Kalatzis V, da Cruz L, Coffey P, Webster AR, Welch E. Functional rescue of REP1 following treatment with PTC124 and novel derivative PTC-414 in human choroideremia fibroblasts and the nonsense-mediated zebrafish model. Hum Mol Genet. 2016 Aug 15;25(16):3416-3431. doi: 10.1093/hmg/ddw184.
Moosajee M, Gregory-Evans K, Ellis CD, Seabra MC, Gregory-Evans CY. Translational bypass of nonsense mutations in zebrafish rep1, pax2.1 and lamb1 highlights a viable therapeutic option for untreatable genetic eye disease. Hum Mol Genet. 2008 Dec 15;17(24):3987-4000
Guerin K, Gregory-Evans CY, Hodges MD, Moosajee M, Mackay DS, Gregory-Evans K, Flannery JG. Systemic aminoglycoside treatment in rodent models of retinitis pigmentosa. Exp Eye Res. 2008 Sep;87(3):197-207
Investigating the genetics of congenital eye disorders and inherited retinal disease
Using the latest next generation sequencing technology, including whole exome and whole genome sequencing with extensive bioinformatics, we are identifying the genetic causes of eye disease. Once the genetic cause is established, we use various models such as the induced pluripotent stem cell (iPSC) derived retinal pigment epithelium, photoreceptors and optic cups, to dissect the molecular basis and understand the disease mechanisms in order to develop new therapeutic approaches for treating these conditions. Please watch the video below to see how we can grow an early eye in a petri dish from a patient’s skin cells.
Eastlake K, Heywood WE, Tracey-White D, Aquino E, Bliss E, Vasta GR, Mills K, Khaw PT, Moosajee M, Limb GA. Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration. Sci Rep. 2017 Mar 16;7:44601. doi: 10.1038/srep44601.
Hull S, Owen N, Islam F, Tracey-White D, Plagnol V, Holder G, Michaelides M, Carss K, Raymond L, Rozet J, Ramsden SC, Black GCM, Perrault I, Moosajee M, Webster AR, Arno G, Moore AT. Non-syndromic retinal dystrophy due to bi-allelic mutations in the ciliary transport gene IFT140. Invest Ophthalmol Vis Sci 2016 Mar 1;57(3):1053-62
Moosajee M, Yu-Wai-Man P, Rouzier C, Bitner-Glindzicz M, Bowman R. Clinical utility gene card for: Wolfram syndrome. Eur J Hum Genet. 2016 Nov;24(11). doi: 10.1038/ejhg.2016.49.
Richardson R, Hingorani M, Van Heyningen V, Gregory-Evans C, Moosajee M. Clinical utility gene card for: Aniridia. Eur J Hum Genet. 2016 Nov;24(11). doi: 10.1038/ejhg.2016.73.
Moosajee M, Ramsden SC, Black GC, Seabra MC, Webster AR. Clinical utility gene card for: Choroideremia. Eur J Hum Genet. 2014 Apr;22(4). doi:10.1038/ejhg.2013.183.
Viringipurampeer IA, Ferreira T, DeMaria S, Yoon JJ, Moosajee M, Gregory-Evans K, Ngai J, Gregory-Evans CY. Pax2 regulates a Fadd-dependent cellular switch that drives tissue fusion during eye development. Hum Mol Genet. 2012 May 15;21(10):2357-69
Gregory-Evans CY, Moosajee M, Shan X, Gregory-Evans K. Gene-specific differential response to anti-apoptotic therapies in zebrafish models of ocular coloboma. Mol Vis. 2011; 17:1473-1484
Moosajee M, Tulloch M, Baron R, Gregory-Evans CY, Pereira-Leal JB, Seabra MC. Single choroideremia gene in non-mammalian vertebrates explains early embryonic lethality of the zebrafish model of choroideraemia. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):3009-16
Gregory-Evans CY, Moosajee M, Hogdes MD, Mackay DS, Vargesson N, Game L, Bloch-Zupan A, Rüschendorf F, Santos-Pinto L, Wackens G, Gregory-Evans K. SNP genome scanning localises oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner ear disease and FADD in ocular coloboma. Hum Mol Genet. 2007 Oct 15;16(20):3482-93
Natural history studies to understand disease progression, identify the optimal therapeutic window and determine reliable outcome measures for clinical trials
At Moorfields Eye Hospital we have a state-of-the-art Clinical Research facility with high-tech imaging equipment that enables us to study the detailed clinical features of eye disease and monitor the progression. We are making advances in our understanding of the relationship between the genetic diagnosis and the clinical presentation, and discovering biomarkers using whole metabolome testing. This allows us to screen all the metabolites in an individual’s blood so we can use them as markers for response to drug treatments in clinical trials.
Moosajee M, Abbouda A, Foot B, Bunce C, Moore AT, Acheson J. Active surveillance of choroidal neovascularisation in children; Incidence, aetiology and management findings from a national study in the United Kingdom. Br J Ophthal. 2017 Aug 26. doi: 10.1136/bjophthalmol-2017- 310445
Abbouda A, Dubis A, Webster AR, Moosajee M. Identifying characteristic features of the retinal and choroidal vasculature in Choroideremia using optical coherence tomography angiography. Eye (Lond). 2017 Nov 17. doi: 10.1038/eye.2017.242
Abbouda A, Lim W, Sporogyte L, Webster AR, Moosajee M. Quantitative and qualitative features of spectral domain optical coherence tomography provide prognostic indicators for visual acuity in choroideremia patients. Ophthalmic Surg Lasers Imaging Retina 2017 Sep 1;48(9):711-716.
Moosajee M, Ramsden SC, Black GC, Moore AT, Webster A. Spectrum of CHM mutations, structural retinal features and their progression in choroideremia patients within the UK. Invest. Ophthalmol. Vis. Sci. 2014 55:6431
Gregory-Evans K, Cheong-Leen R, George SM, Xie J, Moosajee M, Colapinto P, Gregory-Evans CY. Non-invasive anterior segment and posterior segment optical coherence tomography and phenotypic characterization of aniridia. Can J Ophth 2011 Aug; 46(4):337-44
Dr Mariya Moosajee’s Lab
Dr Maria Toms, Research Associate
Dr Nick Owens, Research Associate
Dr Rodrigo Young, Research Associate
Dr Ahmed Hagag, Clinical Research Fellow
Dr Andreas Mitsios, Clinical Research Fellow
Ms Dhani Tracey-White, Research Assistant
Ms Constance Maurer, Research Assistant
Maria Toms, completed 2018
Dr Rose Richardson, Research Associate
Dr Matthew Smart, Research Associate
Dr Alessandro Abbouda, Clinical Research Fellow
Prizes achieved from members of Dr Mariya Moosajee’s Research Group
|2018||Prize for Best Presentation at the UCL FLMS postdoctoral research and careers symposium
Awarded to Rose Richardson, Research Associate
|2018||International Usher syndrome conference 2018 Travel Award for an excellent paper
Awarded to Maria Toms, Research Associate
|2017||The Societas Ophthalmologica Europæa (SOE) Prize
Royal College of Ophthalmologists Annual Congress, Liverpool
Awarded to Adam Ali, Medical Student in the Moosajee lab
|2016||The UK Eye Genetics Group Best Poster Prize
UK Eye Genetic Group Annual Conference 2016
Awarded to Dr Alessandro Abbouda, Clinical Research Fellow
Telephone: +44 (020) 7556 2260
Dr Mariya Moosajee
Development, Ageing and Disease
UCL Institute of Ophthalmology
11-43 Bath Street